"Hear me clearly: America is not a racist country," Scott said.
"It's backwards to fight discrimination with different types of discrimination, and it's wrong to try to use our painful past to dishonestly shut down debates in the present."
The only Black Republican senator, Scott has talked openly about his experience being targeted by police, including getting pulled over seven times in one year.
Now he's leading the GOP effort to pass police reform legislation in the wake of George Floyd's death.
"I have experienced the pain of discrimination," Scott said.
"I get called Uncle Tom, and the N-word by progressives, by liberals," he added.
Scott called out Democrats for using the filibuster last year to block his police reform bill and then this year, when they are in power, claiming the filibuster needs to be abolished because it's a Jim Crow relic.
"The same filibuster that the Democrats used to kill my police reform bill last year has not suddenly become a racist relic," Scott said in defending the Senate 60-vote requirement to advance most legislation.
"Race is not a political weapon to settle every issue the way one side wants," Scott added.
During his 15-minute rebuttal, Scott, a star in the Republican Party, sought to strike an optimistic tone about the progress of America, saying his grandfather in his 94 years "saw his family go from cotton to Congress in one lifetime."
Scott touted former President Trump's record on the economy and on developing vaccines to fight the coronavirus pandemic, and he warned against "socialist dreams" under Biden's administration.
Scott credited Trump's "Operation Warp Speed" for flooding the country with safe and effective vaccines and the bipartisan coronavirus laws that Trump signed into law last year for an economy that is on the rebound.
"This Administration inherited a tide that had already turned," Scott said. "The coronavirus is on the run!"
Scott said while Biden promised unity, the president instead promoted a "partisan wish list" and enacted liberal policies that have driven a wedge.
"Three months in, the actions of this president and his party are pulling us further and further apart," Scott said.
Growing up poor to a single mother who worked long hours as a nurse's assistant, Scott often touts the promise of the American Dream and the perseverance that landed him in Congress.
Scott, 55, has been a strong proponent of school choice to help children in underserved communities have a better chance for success. He said the coronavirus pandemic has revealed the "clearest case for school choice in our lifetimes," as too many public schools are still closed and private and religious schools have reopened.
"Locking vulnerable kids out of the classroom is locking adults out of their future," Scott said. "Our public schools should have reopened months ago."
Scott authored the Opportunity Zones provisions in President Trump's tax cut plan to attract new investments in distressed zip codes. He credited the GOP tax and jobs plans under Trump for establishing the "most inclusive economy in my lifetime" prior to the coronavirus pandemic.
He touted the lowest unemployment rates "ever recorded" for African-Americans, Hispanics, and Asian-Americans, and the lowest rates for women in nearly 70 years.
"That happened because Republicans focused on expanding opportunity for all Americans," Scott said.
He rejected the Democrats' plan for the economy with big government expansion and more spending.
"Our best future won’t come from Washington schemes or socialist dreams," Scott said. "It will come from you — the American people."
Other Republicans took shots at Biden during and after his address to Congress.
"This is the latest Biden has stayed up since November 3," quipped Rep. Nancy Mace, R-S.C.
Republicans have been hammering Biden for reversing Trump's immigration policies and have blamed his rhetoric and executive orders for the crush of migrants flocking to the border. GOP lawmakers accused Biden of whitewashing the border crisis during his speech.
"We have a crisis at the border," House GOP Leader Kevin McCarthy, R-Calif., tweeted. "The President has failed to address it—let alone acknowledge it. It's the Biden Border Crisis, and it's a complete catastrophe."
During his address, Biden outlined his $1.8 trillion American Families Plan to boost childcare, paid family leave and educational opportunities. This proposal is on top of his $2.3 trillion infrastructure proposal.
But leery Republicans raised alarms about more spending on expansive government programs and new tax hikes on the wealthy and corporations to pay for it.
"Someone needs to tell @JoeBiden that money doesn’t grow on trees," tweeted Rep. Diana Harshbarger, R-Tenn.
Rep. Ralph Norman, R-S.C., said Biden's speech reaffirmed his beliefs that Biden just wants to saddle the American people with more debt.
"This President’s agenda is a one way ticket to a welfare state funded by none other than you - the American taxpayer," Norman tweeted.